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Clinical presentation and short-term outcome of endoscopic therapy of patients with symptomatic incomplete pancreas divisum
Clinical presentation and short-term outcome of endoscopic therapy of patients with symptomatic incomplete pancreas divisum Leslie Jacob, MD, Joseph E. Geenen, MD, Marc F. Catalano, MD, G. Kenneth Johnson, MD, Daniel J. Geenen, MD, Walter J. Hogan, MD Milwaukee, Wisconsin
Background: The clinical significance of incomplete pancreas divisum (IPD) has not been fully described. In this study we report the clinical presentation and results of endoscopic treatment of the 32 (0.6%) patients with IPD seen at our center over a 10-year period. Methods: The study population consisted of 24 women and 8 men (mean age 42 years, range 13 to 82 years). Ten (31%) patients presented with acute recurrent pancreatitis, 5 (16%) with chronic pancreatitis, and 3 (9%) with pancreatic type pain. Detailed history, laboratory tests, US, CT, and ERCP excluded other etiologies for their symptoms. The remaining 14 (44%) presented with biliary problems. The 18 symptomatic patients with IPD were treated as follows: 8 received dorsal duct stents, 3 underwent minor papilla endoscopic sphincterotomy and dorsal duct stent placement, 4 had minor papilla dilatation only, and 3 had ventral duct stents placed. Results: Patients were then followed for recurrence of pancreatitis and pancreatic-type pain. Mean follow-up was 15.5 months (range 3 to 30 months). Six (60%) of the patients with acute recurrent pancreatitis and 4 (80%) with chronic pancreatitis benefitted from the endoscopic therapy. However, only 1 (33%) of the patients with pancreatic-type pain benefitted. Conclusion: The clinical presentation and response to endoscopic therapy of patients with ICP appeared to be similar to that of patients with complete pancreas divisum. (Gastrointest Endosc 1999;49:53-7.) Anatomic variations of the pancreatic ducts have been known since the 17th century. The aberrant embryologic events responsible for the ductal anomalies have been identified and several variations have been described, the prototype being pancreas divisum.1-3 This congenital anomaly is caused by failure of fusion of the ventral and dorsal pancreatic anlagen during the 6th and 7th week of gestation. When this occurs, the major portion of the pancreas drains through the minor papilla via the dorsal duct and the ventral duct drains only the small ventral
Received April 1, 1997. For revision August 19, 1997. Accepted July 5, 1998. From the Pancreatic Biliary Center, St. Luke’s Medical Center, Milwaukee, Wisconsin. Reprint requests: Joseph E. Geenen, MD, Gastroenterology Consultants, Ltd., 2801 West Kinnickinnic River Parkway, Suite 570, Milwaukee, WI 53215. Copyright © 1999 by the American Society for Gastrointestinal Endoscopy 0016-5107/99/$8.00 + 0 37/1/92905 VOLUME 49, NO. 1, 1999
pancreas. Incomplete pancreas divisum (IPD) is present when a small communicating branch connects the dorsal and ventral ducts (Fig. 1). Large autopsy series have given estimates that 5% to 10% of the population has pancreas divisum.4 The frequency of IPD ranges from 0.13%5 to 0.9%.6 The clinical pathologic significance of IPD is not well established. There are only rare case reports of acute pancreatitis associated with IPD. In these case reports IPD occurred in association with an abnormal junction of the pancreaticobiliary duct system.7 However, there are also several reports of IPD patients with symptoms unrelated to the pancreas where the IPD was an incidental finding.6,8 There are no reports of endoscopic treatment of symptomatic IPD patients. Recurrent pancreatitis associated with complete pancreas divisum is a well established clinical entity, and randomized trials have shown the benefit of endoscopic therapy in patients with this condition.9,10 Relative obstruction of the flow of pancreatic secretions caused by the tiny opening in the minor papilla is the hypothesis GASTROINTESTINAL ENDOSCOPY
53
L Jacob, J Geenen, M Catalano, et al.
Endoscopic therapy of symptomatic incomplete pancreas divisum
B
A
Figure 1. A, Complete pancreas divisum. B, Incomplete pancreas divisum.
Figure 2. Clinical presentation of IPD patients.
for this association and the basis for endoscopic therapy. Thus, this same hypothesis formed the basis for endoscopic therapy offered to symptomatic IPD patients who were referred to our center. Here we report the clinical presentation and results of endoscopic treatment of IPD patients seen at our referral center over a 10-year period. PATIENTS AND METHODS All new ERCP procedures entered into our data bank from 1984 to 1994 were reviewed. A total of 5647 new ERCPs with pancreatograms were performed during this period. Complete pancreas divisum was found in 482 (9%) 54
GASTROINTESTINAL ENDOSCOPY
of patients and IPD was diagnosed in 32 (0.6%) patients. The records of all 32 IPD patients were then reviewed. There were 24 women and 8 men (mean age of 42 years, range 13 to 82 years). The nature of their symptoms, the clinical presentation and indications for ERCP were noted. Eighteen of these patients were referred with pancreatic problems, acute pancreatitis, pancreatic type pain, and chronic pancreatitis. The remaining 14 patients were referred with biliary problems requiring ERCP and the IPD was an incidental finding (Fig. 2). All patients had undergone a detailed evaluation including appropriate laboratory tests, US, CT, and ERCP to ascertain the etiology of their symptoms. Endoscopic therapy with a goal of decompressing the dorsal duct was performed in the 18 symptomatic IPD patients (Table 1). Dorsal duct stenting alone was performed in 8 patients, 3 underwent minor papilla endoscopic sphincterotomy and dorsal duct stent placement, and 4 had minor papilla dilatation only. In the remaining 3 patients, cannulation of the minor papilla was unsuccessful and therefore they had ventral duct stents placed. Biliary sphincterotomy or ventral duct sphincterotomy was not performed in these 3 patients. By protocol, the patients who received stents (including ventral duct stents) had at least 3 stents placed over a period of 1 year. Two patients had fewer than 2 stents placed: 1 patient refused to undergo further stenting and the other felt well and declined further stent insertion. Of the patients who had dilatation only, 1 patient underwent dilation 3 times and the remaining 2 patients had 2 dilations each. The patients were then followed for recurrence of pancreatitis and pancreatic type pain. This was done at the time of stent change and follow-up office visits, as well as VOLUME 49, NO. 1, 1999
Endoscopic therapy of symptomatic incomplete pancreas divisum
L Jacob, J Geenen, M Catalano, et al.
Table 1. Endoscopic treatment modalities of symptomatic IPD patients Treatment modality Clinical presentation
Number of patients
Stent only
10 3 5
4 2 2
Acute recurrent pancreatitis Pancreatic-type pain Chronic pancreatitis
Dorsal duct ES+ Stent
Dil only
Ventral duct Stent only
3 1 —
1 — 2
2 — 1
ES, Endoscopic sphincterotomy; Dil, dilation.
by telephone interview. The mean follow-up was 15.5 months (range 3 to 30 months); 4 patients could not be reached for follow-up.
Table 2. Clinical benefits of endoscopic treatment of symptomatic IPD patients Clinical benefit
RESULTS All 32 patients with IPD were referred with a specific pancreaticobiliary problem that required diagnostic or therapeutic ERCP. Of these, 18 were referred with pancreatic problems, acute pancreatitis, acute recurrent pancreatitis, pancreatic type pain and/or chronic pancreatitis. The remaining 14 were referred with biliary problems requiring ERCP, and IPD was an incidental finding (Fig. 2). The biliary problems included bile duct stones, primary sclerosing cholangitis, bile duct stricture, and choledochocele. Acute recurrent pancreatitis (ARP) was the clinical presentation in 10 (31%) of patients. ARP was defined as two or more episodes of abdominal pain with twice normal elevations of serum amylase. No other abnormality or etiology for pancreatitis other than IPD was found in these patients. Pancreatic type pain was the presenting complaint in 3 (9%) patients. Other causes of abdominal pain were excluded by a detailed clinical evaluation, laboratory tests, and radiologic studies. Chronic pancreatitis was diagnosed in 5 (16%) of the patients based on radiologic and ERCP criteria. Again, no other etiology for the chronic pancreatitis was found in these patients. In the ARP group, 6 (60%) of the 10 patients benefitted from the endoscopic therapy (Table 2). Of the 4 (40%) who had recurrence of symptoms, 3 had pancreatitis and 1 had pancreatic type pain only. None of these recurrences were associated with stent occlusion or migration. In the pancreatic pain group, only 1 (33%) of the 3 patients benefitted from endoscopic therapy (Table 2). However, in 1 of 2 patients who continued to have pain, the pain was associated with an occluded stent. In the chronic pancreatitis group, 4 (80%) of the 5 patients benefitted from endoscopic treatment (Table 2). One of these patients required stricture dilatation before stent placement. The single patient in this group who did not benefit continVOLUME 49, NO. 1, 1999
Clinical presentation
Patient (n)
Acute recurrent pancreatitis Pancreatic-type pain Chronic pancreatitis
10 3 5
Yes 6 (60%) 1 (33%) 4 (80%)
No 4 (40%) 2 (67%) 1 (20%)
ued to have pain and amylase elevation that were not associated with stent occlusion or migration. Dorsal duct stenting alone was effective in 5 of the 8 patients with no further recurrence of symptoms. All 3 patients who had ventral duct stents had no recurrence of symptoms. Two of the 3 who underwent minor papilla endoscopic sphincterotomy and dorsal duct stenting had recurrence of symptoms. Two of the 3 patients who had only minor papilla dilatation had recurrent symptoms. One patient in the study developed mild pancreatitis post-ERCP. A total of 9 stents were occluded but only 1 patient had symptoms associated with stent occlusion. During follow-up, 1 patient eventually underwent a Puestow pancreaticojejunostomy; 2 others had partial pancreatectomies. One patient in the pain group was eventually referred for pain management. DISCUSSION Complete pancreas divisum is a well-recognized congenital anomaly. It is estimated to be present in 5% to 10% of the population autopsy data4 and is encountered in 1.3% to 8% of ERCP studies.11,12 Although most patients with complete pancreas divisum may be asymptomatic, there are several reports in which acute pancreatitis, pancreatic type pain, and chronic pancreatitis were associated with this anomaly.14,15 The etiology of these symptoms is thought to be minor papilla stenosis compromising the outflow of pancreatic juice into the duodenum.13-15 Randomized trials based on this obstruction to flow hypothesis have shown that decompression of the dorsal duct, either by minor papilla endoGASTROINTESTINAL ENDOSCOPY
55
L Jacob, J Geenen, M Catalano, et al.
Endoscopic therapy of symptomatic incomplete pancreas divisum
scopic sphincterotomy and/or stenting the minor papilla, leads to objective improvement in symptoms in patients with recurrent pancreatitis associated with complete pancreas divisum.9,10 Incomplete pancreas divisum (IPD), in contrast to complete divisum, has not been well defined and its clinical significance is unclear. Sugawa et al.6 suggested an incidence in the range of 0.13%5 to 0.9%.6 This may be partly due to under-reporting or failure to recognize the anomaly. The small connecting branch may not be visualized, especially if the ventral ductal system is inadequately opacified. There are only rare case reports of symptoms associated with IPD.7 However, there are several reports in which IPD was an incidental finding.6.8 It is conceivable that the small communicating branch provides additional drainage of the dorsal duct and thus fewer patients have symptoms. There are also no reports of endoscopic therapy of symptomatic IPD patients. We reviewed all the new ERCPs with pancreatograms performed at our center over a 10-year period. The 9% incidence of complete pancreas divisum and 0.6% incidence of IPD is comparable to previous reports. The most common presenting clinical condition associated with IPD was acute recurrent pancreatitis (ARP) (31%) followed by chronic pancreatitis (16%) and pancreatic-type pain (9%). That is, 56% of patients with IPD had clinical manifestations related to the anomaly. Thorough diagnostic evaluations eliminated other causes for their symptoms. Therefore, the clinical presentations of these patients are similar to those of patients with complete pancreas divisum. Conceivably, the obstruction to flow is the underlying cause for these symptoms in IPD patients, the additional drainage via the ventral system through the small communicating branch being inadequate to prevent symptoms. However, in the event of failure to cannulate and stent the dorsal duct, a stent placed in the ventral duct could decompress the dorsal system via the small communicating branch. Several treatment modalities have been advocated for patients with symptomatic complete pancreas divisum. The goal of each of these modalities is to improve flow rate at the minor papilla and decompress the dorsal duct. Surgical sphincteroplasty with minor only or both major and minor septoplasty is often performed. Warshaw et al.16 performed similar procedures in 88 patients presenting with acute recurrent pancreatitis and pancreatic type pain associated with complete pancreas divisum. There was an overall 70% improvement at a mean follow-up of 53 months. Restenosis and changes of chronic pancreatitis were reported postoperatively.16 Endoscopic treatment of symptomatic com-
plete pancreas divisum patients has included minor papilla endoscopic sphincterotomy with short periods of stenting and dilatation of minor papilla and stenting alone without endoscopic sphincterotomy. Restenosis of the minor papilla after endoscopic sphincterotomy, severe pancreatitis, stent occlusion, stent-induced ductal changes, and stent migration are some of the complications of endoscopic treatment. The 18 symptomatic IPD patients reported in this study were treated endoscopically with the use of various approaches. These included stent only, endoscopic sphincterotomy of the minor papilla and stent, and dilatation of the minor papilla only. The ventral duct was stented in 3 patients in whom the minor papilla could not be cannulated. The goal of these various approaches was to decompress the dorsal duct via the minor papilla or the ventral duct. Significant clinical benefit in terms of recurrent pancreatitis and pancreatic type pain was achieved in the subgroups with acute recurrent pancreatitis and chronic pancreatitis during the short-term follow-up. Six of the patients (60%) in the acute recurrent pancreatitis group benefitted from the endoscopic treatment. This response rate is comparable to the endoscopic treatment of acute recurrent pancreatitis patients associated with complete pancreas divisum, as reported by Lans9 and Lehman10 and their associates. It is interesting to note that the patients with chronic pancreatitis and IPD had significant clinical improvement, whereas patients with chronic pancreatitis associated with complete pancreas divisum do not respond well to endoscopic treatment.10 The poor response of patients with IPD and pain alone in the pain group is similar to that for patients with complete pancreas divisum. Stent occlusion did not play a major role in the recurrence of symptoms or failure or treatment. In evaluating the outcome of the various endoscopic techniques used, dorsal duct stenting alone achieved the best results. Five of the 8 patients who had dorsal duct stents alone had no recurrence of their symptoms. It is also interesting that all 3 patients who had ventral duct stents had no recurrence of their symptoms. Two of the 3 patients in both the minor papilla endoscopic sphincterotomy and stent group and minor papilla dilatation only group had recurrence of symptoms. Restenosis of the minor papilla was not noted in the endoscopic sphincterotomy group. Complications were minimal: 1 mild post-ERCP pancreatitis, no stent migration, and only mild-tomoderate stent-induced ductal changes. As expected, all 9 cases of stent occlusion were in the stent alone group because stents were in place for longer durations of time in this group. In conclusion, significant pancreatic disorders occurred in 56% of patients with IPD. Dorsal duct
56
GASTROINTESTINAL ENDOSCOPY
VOLUME 49, NO. 1, 1999
Endoscopic therapy of symptomatic incomplete pancreas divisum
L Jacob, J Geenen, M Catalano, et al.
decompression is beneficial in IPD patients with acute recurrent pancreatitis or chronic pancreatitis. Patients with only pancreatic type pain are less likely to benefit from endoscopic therapy. The clinical significance of IPD may be similar to that of complete pancreas divisum.
8. Moreira VF, Merono E, Ledo L. Incomplete pancreas divisum. Gastrointest Endosc 1991;37:104-5. 9. Lans, JI, Geenen JE, Johanson JF. Endoscopic therapy in patients with pancreas divisum find acute pancreatitis: a prospective, randomized, controlled clinical trial. Gastrointest Endosc 1992;38:430-4. 10. Lehman GA, Sherman S, Nisi R, Hawes RH. Pancreas divisum: results of minor papilla sphincterotomy. Gastrointest Endosc 1993;39:1-8. 11. Satterfield ST, McCarthy JH, Geenen JE, Hogan WJ, Venu RP, Dodds WJ, et al. Clinical experience in 82 patients with pancreas divisum: preliminary results of manometry and endoscopic therapy. Pancreas 1988;3:248-53. 12. Bernard JP, Sahel J, Giovanni M. Pancreas divisum is a probable cause of acute pancreatitis: a report of 132 cases. Pancreas 1990;5:248-54. 13. Geenen JE. ASGE distinguished lecture—endoscopic therapy of pancreatic disease: a new horizon. Gastrointest Endosc 1988;34:380-9. 14. Gregg JA. Pancreas divisum: its association with pancreatitis. Am J Surg 1977;134:539-43. 15. Cotton PB. Congenital anomaly of pancreas divisum as cause of obstructive pain and pancreatitis. Gut 1980;21:105-14. 16. Warshaw AL, Simeone JF, Schapiro RH, et al. Evaluation and treatment of the dominant dorsal duct syndrome (pancreas divisum redefined). Am J Surg 1990;159:59-64.
REFERENCES 1. Kleitsch WP. Anatomy of the pancreas: study with special reference to duct system. Arch Surg 1955;71:795-802. 2. Mac Carty RL, Stephens DH, Brown AL, Carlson HC. Retrograde pancreatography in autopsy specimens. Am J Roentgen Rad Nucl Med 1975;123:359-66. 3. Rienhoff WF, Pickrell KL. Pancreatitis—an anatomic study of the pancreatic and extrahepatic, biliary systems. Arch Surg 1945;51:205-19. 4. Dawson W, Langman J. An anatomic radiologic study on pancreatic duct pattern in man. Anat Rec 1961;39:59-68. 5. Tulassay Z, Papp J, Farkas IE. Diagnostic aspects of incomplete pancreas divisum [letter]. Gastrointest Endosc 1986;32:428. 6. Sugawa CH, Alexander JW, Nunez DC. Pancreas divisum: Is it a normal anatomic variant? Am J Surg 1987;153:62-7. 7. Ng JWD, Wong MK, Huang J. Incomplete pancreas divisum associated with abnormal junction of pancreaticobiliary duct system. Gastrointest Endosc 1992;38:105-6.
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VOLUME 49, NO. 1, 1999
GASTROINTESTINAL ENDOSCOPY
57
Background: The clinical significance of incomplete pancreas divisum (IPD) has not been fully described. In this study we report the clinical presentation and results of endoscopic treatment of the 32 (0.6%) patients with IPD seen at our center over a 10-year period. Methods: The study population consisted of 24 women and 8 men (mean age 42 years, range 13 to 82 years). Ten (31%) patients presented with acute recurrent pancreatitis, 5 (16%) with chronic pancreatitis, and 3 (9%) with pancreatic type pain. Detailed history, laboratory tests, US, CT, and ERCP excluded other etiologies for their symptoms. The remaining 14 (44%) presented with biliary problems. The 18 symptomatic patients with IPD were treated as follows: 8 received dorsal duct stents, 3 underwent minor papilla endoscopic sphincterotomy and dorsal duct stent placement, 4 had minor papilla dilatation only, and 3 had ventral duct stents placed. Results: Patients were then followed for recurrence of pancreatitis and pancreatic-type pain. Mean follow-up was 15.5 months (range 3 to 30 months). Six (60%) of the patients with acute recurrent pancreatitis and 4 (80%) with chronic pancreatitis benefitted from the endoscopic therapy. However, only 1 (33%) of the patients with pancreatic-type pain benefitted. Conclusion: The clinical presentation and response to endoscopic therapy of patients with ICP appeared to be similar to that of patients with complete pancreas divisum. (Gastrointest Endosc 1999;49:53-7.) Anatomic variations of the pancreatic ducts have been known since the 17th century. The aberrant embryologic events responsible for the ductal anomalies have been identified and several variations have been described, the prototype being pancreas divisum.1-3 This congenital anomaly is caused by failure of fusion of the ventral and dorsal pancreatic anlagen during the 6th and 7th week of gestation. When this occurs, the major portion of the pancreas drains through the minor papilla via the dorsal duct and the ventral duct drains only the small ventral
Received April 1, 1997. For revision August 19, 1997. Accepted July 5, 1998. From the Pancreatic Biliary Center, St. Luke’s Medical Center, Milwaukee, Wisconsin. Reprint requests: Joseph E. Geenen, MD, Gastroenterology Consultants, Ltd., 2801 West Kinnickinnic River Parkway, Suite 570, Milwaukee, WI 53215. Copyright © 1999 by the American Society for Gastrointestinal Endoscopy 0016-5107/99/$8.00 + 0 37/1/92905 VOLUME 49, NO. 1, 1999
pancreas. Incomplete pancreas divisum (IPD) is present when a small communicating branch connects the dorsal and ventral ducts (Fig. 1). Large autopsy series have given estimates that 5% to 10% of the population has pancreas divisum.4 The frequency of IPD ranges from 0.13%5 to 0.9%.6 The clinical pathologic significance of IPD is not well established. There are only rare case reports of acute pancreatitis associated with IPD. In these case reports IPD occurred in association with an abnormal junction of the pancreaticobiliary duct system.7 However, there are also several reports of IPD patients with symptoms unrelated to the pancreas where the IPD was an incidental finding.6,8 There are no reports of endoscopic treatment of symptomatic IPD patients. Recurrent pancreatitis associated with complete pancreas divisum is a well established clinical entity, and randomized trials have shown the benefit of endoscopic therapy in patients with this condition.9,10 Relative obstruction of the flow of pancreatic secretions caused by the tiny opening in the minor papilla is the hypothesis GASTROINTESTINAL ENDOSCOPY
53
L Jacob, J Geenen, M Catalano, et al.
Endoscopic therapy of symptomatic incomplete pancreas divisum
B
A
Figure 1. A, Complete pancreas divisum. B, Incomplete pancreas divisum.
Figure 2. Clinical presentation of IPD patients.
for this association and the basis for endoscopic therapy. Thus, this same hypothesis formed the basis for endoscopic therapy offered to symptomatic IPD patients who were referred to our center. Here we report the clinical presentation and results of endoscopic treatment of IPD patients seen at our referral center over a 10-year period. PATIENTS AND METHODS All new ERCP procedures entered into our data bank from 1984 to 1994 were reviewed. A total of 5647 new ERCPs with pancreatograms were performed during this period. Complete pancreas divisum was found in 482 (9%) 54
GASTROINTESTINAL ENDOSCOPY
of patients and IPD was diagnosed in 32 (0.6%) patients. The records of all 32 IPD patients were then reviewed. There were 24 women and 8 men (mean age of 42 years, range 13 to 82 years). The nature of their symptoms, the clinical presentation and indications for ERCP were noted. Eighteen of these patients were referred with pancreatic problems, acute pancreatitis, pancreatic type pain, and chronic pancreatitis. The remaining 14 patients were referred with biliary problems requiring ERCP and the IPD was an incidental finding (Fig. 2). All patients had undergone a detailed evaluation including appropriate laboratory tests, US, CT, and ERCP to ascertain the etiology of their symptoms. Endoscopic therapy with a goal of decompressing the dorsal duct was performed in the 18 symptomatic IPD patients (Table 1). Dorsal duct stenting alone was performed in 8 patients, 3 underwent minor papilla endoscopic sphincterotomy and dorsal duct stent placement, and 4 had minor papilla dilatation only. In the remaining 3 patients, cannulation of the minor papilla was unsuccessful and therefore they had ventral duct stents placed. Biliary sphincterotomy or ventral duct sphincterotomy was not performed in these 3 patients. By protocol, the patients who received stents (including ventral duct stents) had at least 3 stents placed over a period of 1 year. Two patients had fewer than 2 stents placed: 1 patient refused to undergo further stenting and the other felt well and declined further stent insertion. Of the patients who had dilatation only, 1 patient underwent dilation 3 times and the remaining 2 patients had 2 dilations each. The patients were then followed for recurrence of pancreatitis and pancreatic type pain. This was done at the time of stent change and follow-up office visits, as well as VOLUME 49, NO. 1, 1999
Endoscopic therapy of symptomatic incomplete pancreas divisum
L Jacob, J Geenen, M Catalano, et al.
Table 1. Endoscopic treatment modalities of symptomatic IPD patients Treatment modality Clinical presentation
Number of patients
Stent only
10 3 5
4 2 2
Acute recurrent pancreatitis Pancreatic-type pain Chronic pancreatitis
Dorsal duct ES+ Stent
Dil only
Ventral duct Stent only
3 1 —
1 — 2
2 — 1
ES, Endoscopic sphincterotomy; Dil, dilation.
by telephone interview. The mean follow-up was 15.5 months (range 3 to 30 months); 4 patients could not be reached for follow-up.
Table 2. Clinical benefits of endoscopic treatment of symptomatic IPD patients Clinical benefit
RESULTS All 32 patients with IPD were referred with a specific pancreaticobiliary problem that required diagnostic or therapeutic ERCP. Of these, 18 were referred with pancreatic problems, acute pancreatitis, acute recurrent pancreatitis, pancreatic type pain and/or chronic pancreatitis. The remaining 14 were referred with biliary problems requiring ERCP, and IPD was an incidental finding (Fig. 2). The biliary problems included bile duct stones, primary sclerosing cholangitis, bile duct stricture, and choledochocele. Acute recurrent pancreatitis (ARP) was the clinical presentation in 10 (31%) of patients. ARP was defined as two or more episodes of abdominal pain with twice normal elevations of serum amylase. No other abnormality or etiology for pancreatitis other than IPD was found in these patients. Pancreatic type pain was the presenting complaint in 3 (9%) patients. Other causes of abdominal pain were excluded by a detailed clinical evaluation, laboratory tests, and radiologic studies. Chronic pancreatitis was diagnosed in 5 (16%) of the patients based on radiologic and ERCP criteria. Again, no other etiology for the chronic pancreatitis was found in these patients. In the ARP group, 6 (60%) of the 10 patients benefitted from the endoscopic therapy (Table 2). Of the 4 (40%) who had recurrence of symptoms, 3 had pancreatitis and 1 had pancreatic type pain only. None of these recurrences were associated with stent occlusion or migration. In the pancreatic pain group, only 1 (33%) of the 3 patients benefitted from endoscopic therapy (Table 2). However, in 1 of 2 patients who continued to have pain, the pain was associated with an occluded stent. In the chronic pancreatitis group, 4 (80%) of the 5 patients benefitted from endoscopic treatment (Table 2). One of these patients required stricture dilatation before stent placement. The single patient in this group who did not benefit continVOLUME 49, NO. 1, 1999
Clinical presentation
Patient (n)
Acute recurrent pancreatitis Pancreatic-type pain Chronic pancreatitis
10 3 5
Yes 6 (60%) 1 (33%) 4 (80%)
No 4 (40%) 2 (67%) 1 (20%)
ued to have pain and amylase elevation that were not associated with stent occlusion or migration. Dorsal duct stenting alone was effective in 5 of the 8 patients with no further recurrence of symptoms. All 3 patients who had ventral duct stents had no recurrence of symptoms. Two of the 3 who underwent minor papilla endoscopic sphincterotomy and dorsal duct stenting had recurrence of symptoms. Two of the 3 patients who had only minor papilla dilatation had recurrent symptoms. One patient in the study developed mild pancreatitis post-ERCP. A total of 9 stents were occluded but only 1 patient had symptoms associated with stent occlusion. During follow-up, 1 patient eventually underwent a Puestow pancreaticojejunostomy; 2 others had partial pancreatectomies. One patient in the pain group was eventually referred for pain management. DISCUSSION Complete pancreas divisum is a well-recognized congenital anomaly. It is estimated to be present in 5% to 10% of the population autopsy data4 and is encountered in 1.3% to 8% of ERCP studies.11,12 Although most patients with complete pancreas divisum may be asymptomatic, there are several reports in which acute pancreatitis, pancreatic type pain, and chronic pancreatitis were associated with this anomaly.14,15 The etiology of these symptoms is thought to be minor papilla stenosis compromising the outflow of pancreatic juice into the duodenum.13-15 Randomized trials based on this obstruction to flow hypothesis have shown that decompression of the dorsal duct, either by minor papilla endoGASTROINTESTINAL ENDOSCOPY
55
L Jacob, J Geenen, M Catalano, et al.
Endoscopic therapy of symptomatic incomplete pancreas divisum
scopic sphincterotomy and/or stenting the minor papilla, leads to objective improvement in symptoms in patients with recurrent pancreatitis associated with complete pancreas divisum.9,10 Incomplete pancreas divisum (IPD), in contrast to complete divisum, has not been well defined and its clinical significance is unclear. Sugawa et al.6 suggested an incidence in the range of 0.13%5 to 0.9%.6 This may be partly due to under-reporting or failure to recognize the anomaly. The small connecting branch may not be visualized, especially if the ventral ductal system is inadequately opacified. There are only rare case reports of symptoms associated with IPD.7 However, there are several reports in which IPD was an incidental finding.6.8 It is conceivable that the small communicating branch provides additional drainage of the dorsal duct and thus fewer patients have symptoms. There are also no reports of endoscopic therapy of symptomatic IPD patients. We reviewed all the new ERCPs with pancreatograms performed at our center over a 10-year period. The 9% incidence of complete pancreas divisum and 0.6% incidence of IPD is comparable to previous reports. The most common presenting clinical condition associated with IPD was acute recurrent pancreatitis (ARP) (31%) followed by chronic pancreatitis (16%) and pancreatic-type pain (9%). That is, 56% of patients with IPD had clinical manifestations related to the anomaly. Thorough diagnostic evaluations eliminated other causes for their symptoms. Therefore, the clinical presentations of these patients are similar to those of patients with complete pancreas divisum. Conceivably, the obstruction to flow is the underlying cause for these symptoms in IPD patients, the additional drainage via the ventral system through the small communicating branch being inadequate to prevent symptoms. However, in the event of failure to cannulate and stent the dorsal duct, a stent placed in the ventral duct could decompress the dorsal system via the small communicating branch. Several treatment modalities have been advocated for patients with symptomatic complete pancreas divisum. The goal of each of these modalities is to improve flow rate at the minor papilla and decompress the dorsal duct. Surgical sphincteroplasty with minor only or both major and minor septoplasty is often performed. Warshaw et al.16 performed similar procedures in 88 patients presenting with acute recurrent pancreatitis and pancreatic type pain associated with complete pancreas divisum. There was an overall 70% improvement at a mean follow-up of 53 months. Restenosis and changes of chronic pancreatitis were reported postoperatively.16 Endoscopic treatment of symptomatic com-
plete pancreas divisum patients has included minor papilla endoscopic sphincterotomy with short periods of stenting and dilatation of minor papilla and stenting alone without endoscopic sphincterotomy. Restenosis of the minor papilla after endoscopic sphincterotomy, severe pancreatitis, stent occlusion, stent-induced ductal changes, and stent migration are some of the complications of endoscopic treatment. The 18 symptomatic IPD patients reported in this study were treated endoscopically with the use of various approaches. These included stent only, endoscopic sphincterotomy of the minor papilla and stent, and dilatation of the minor papilla only. The ventral duct was stented in 3 patients in whom the minor papilla could not be cannulated. The goal of these various approaches was to decompress the dorsal duct via the minor papilla or the ventral duct. Significant clinical benefit in terms of recurrent pancreatitis and pancreatic type pain was achieved in the subgroups with acute recurrent pancreatitis and chronic pancreatitis during the short-term follow-up. Six of the patients (60%) in the acute recurrent pancreatitis group benefitted from the endoscopic treatment. This response rate is comparable to the endoscopic treatment of acute recurrent pancreatitis patients associated with complete pancreas divisum, as reported by Lans9 and Lehman10 and their associates. It is interesting to note that the patients with chronic pancreatitis and IPD had significant clinical improvement, whereas patients with chronic pancreatitis associated with complete pancreas divisum do not respond well to endoscopic treatment.10 The poor response of patients with IPD and pain alone in the pain group is similar to that for patients with complete pancreas divisum. Stent occlusion did not play a major role in the recurrence of symptoms or failure or treatment. In evaluating the outcome of the various endoscopic techniques used, dorsal duct stenting alone achieved the best results. Five of the 8 patients who had dorsal duct stents alone had no recurrence of their symptoms. It is also interesting that all 3 patients who had ventral duct stents had no recurrence of their symptoms. Two of the 3 patients in both the minor papilla endoscopic sphincterotomy and stent group and minor papilla dilatation only group had recurrence of symptoms. Restenosis of the minor papilla was not noted in the endoscopic sphincterotomy group. Complications were minimal: 1 mild post-ERCP pancreatitis, no stent migration, and only mild-tomoderate stent-induced ductal changes. As expected, all 9 cases of stent occlusion were in the stent alone group because stents were in place for longer durations of time in this group. In conclusion, significant pancreatic disorders occurred in 56% of patients with IPD. Dorsal duct
56
GASTROINTESTINAL ENDOSCOPY
VOLUME 49, NO. 1, 1999
Endoscopic therapy of symptomatic incomplete pancreas divisum
L Jacob, J Geenen, M Catalano, et al.
decompression is beneficial in IPD patients with acute recurrent pancreatitis or chronic pancreatitis. Patients with only pancreatic type pain are less likely to benefit from endoscopic therapy. The clinical significance of IPD may be similar to that of complete pancreas divisum.
8. Moreira VF, Merono E, Ledo L. Incomplete pancreas divisum. Gastrointest Endosc 1991;37:104-5. 9. Lans, JI, Geenen JE, Johanson JF. Endoscopic therapy in patients with pancreas divisum find acute pancreatitis: a prospective, randomized, controlled clinical trial. Gastrointest Endosc 1992;38:430-4. 10. Lehman GA, Sherman S, Nisi R, Hawes RH. Pancreas divisum: results of minor papilla sphincterotomy. Gastrointest Endosc 1993;39:1-8. 11. Satterfield ST, McCarthy JH, Geenen JE, Hogan WJ, Venu RP, Dodds WJ, et al. Clinical experience in 82 patients with pancreas divisum: preliminary results of manometry and endoscopic therapy. Pancreas 1988;3:248-53. 12. Bernard JP, Sahel J, Giovanni M. Pancreas divisum is a probable cause of acute pancreatitis: a report of 132 cases. Pancreas 1990;5:248-54. 13. Geenen JE. ASGE distinguished lecture—endoscopic therapy of pancreatic disease: a new horizon. Gastrointest Endosc 1988;34:380-9. 14. Gregg JA. Pancreas divisum: its association with pancreatitis. Am J Surg 1977;134:539-43. 15. Cotton PB. Congenital anomaly of pancreas divisum as cause of obstructive pain and pancreatitis. Gut 1980;21:105-14. 16. Warshaw AL, Simeone JF, Schapiro RH, et al. Evaluation and treatment of the dominant dorsal duct syndrome (pancreas divisum redefined). Am J Surg 1990;159:59-64.
REFERENCES 1. Kleitsch WP. Anatomy of the pancreas: study with special reference to duct system. Arch Surg 1955;71:795-802. 2. Mac Carty RL, Stephens DH, Brown AL, Carlson HC. Retrograde pancreatography in autopsy specimens. Am J Roentgen Rad Nucl Med 1975;123:359-66. 3. Rienhoff WF, Pickrell KL. Pancreatitis—an anatomic study of the pancreatic and extrahepatic, biliary systems. Arch Surg 1945;51:205-19. 4. Dawson W, Langman J. An anatomic radiologic study on pancreatic duct pattern in man. Anat Rec 1961;39:59-68. 5. Tulassay Z, Papp J, Farkas IE. Diagnostic aspects of incomplete pancreas divisum [letter]. Gastrointest Endosc 1986;32:428. 6. Sugawa CH, Alexander JW, Nunez DC. Pancreas divisum: Is it a normal anatomic variant? Am J Surg 1987;153:62-7. 7. Ng JWD, Wong MK, Huang J. Incomplete pancreas divisum associated with abnormal junction of pancreaticobiliary duct system. Gastrointest Endosc 1992;38:105-6.
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